Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI

Santander, Nicolás; Contreras-Duarte, Susana; Fernand, María F. Awad; Lizama, Carlos O; Passalacqua, Isabella; Rigotti, Attilio; Busso, Dolores

doi:10.1093/hmg/ddt129

Cited by 6 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(3) Cholesterol in embryonic and fetal development Several human malformation syndromes as well as animal models of pharmacological or genetic blockade of the mevalonate pathway show that cholesterol is absolutely required for normal prenatal development (Porter, 2003). These syndromes most likely result from structural, endocrine and/or signalling abnormalities derived from cholesterol deficiency (Willnow, Hammes & Eaton, 2007;Steinhauer & Treisman, 2009;Santander et al, 2012). However, it is plausible that reduction and/or accumulation of other mevalonate pathway metabolites also play a role.…”

Section: (D) Relationship Between Cns Apolipoprotein E4 Cholesterol mentioning

confidence: 99%

Retracted: Advances in the physiological and pathological implications of cholesterol

et al. 2013

View full text Add to dashboard Cite

Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

show abstract

Section: (D) Relationship Between Cns Apolipoprotein E4 Cholesterol mentioning

confidence: 99%

Retracted: Advances in the physiological and pathological implications of cholesterol

et al. 2013

View full text Add to dashboard Cite

show abstract

“…[ 9 ] (4) Loss-of-function variants that raise (endothelial lipase) [ 10 ] or lower (adenosine triphosphate (ATP) binding cassette transporter subfamily A member 1 (ABCA1)) [ 9 ] HDL-C levels are not associated with reduced or increased ASCVD risk, respectively [ 9 ]. (5) Niacin therapy and CETP inhibition raise HDL-C but do not reduce ASCVD events [ 11 , 12 , 13 , 14 ]. Although niacin therapy reduced ASCVD in the Coronary Drug Project [ 15 ], in patients receiving a statin, niacin increased HDL-C from 35 mg/dL (0.91 mM) to 42 mg/dL (1.08 mM) but did not elicit a demonstrable ASCVD benefit in patients presenting with two components of metabolic syndrome (MetS)—hypertriglyceridemia and a low HDL-C concentration.…”

Section: Introductionmentioning

confidence: 99%

The Alcohol–High-Density Lipoprotein Athero-Protective Axis

et al. 2020

View full text Add to dashboard Cite

Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. More recent evidence has accrued against the hypothesis that raising plasma HDL concentrations prevents ASCVD so that other metabolic processes associated with alcohol consumption have been considered. This review explored the roles of other metabolites induced by alcohol consumption—triglyceride-rich lipoproteins, non-esterified free fatty acids, and acetate, the terminal alcohol metabolite in athero-protection: Current evidence suggests that acetate has a key role in athero-protection but additional studies are needed.

show abstract

“…SR‐BI is a bona fide HDL receptor that mediates selective cholesterol uptake in the liver, macrophages, and steroidogenic tissues . In mice, SR‐BI gene deletion results in elevated HDL levels along with increased atherosclerosis susceptibility and reproductive and developmental defects . In the intestine, SR‐BI is present in the cell surface of enterocytes with an apical to basolateral and cephalic to caudal decreasing expression gradient …”

Section: Introductionmentioning

confidence: 99%

Insulin increases cholesterol uptake, lipid droplet content, and apolipoprotein B secretion in CaCo‐2 cells by upregulating SR‐BI via a PI3K, AKT, and mTOR‐dependent pathway

Fuentes

Santander

Cortés

2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

The actions of insulin on intestinal cholesterol absorption and lipoprotein secretion are not well understood. Herein, we determined the effects of insulin on the levels of cholesterol transporter scavenger receptor, class B, type I (SR‐BI), cellular cholesterol uptake, intracellular lipid accumulation, and lipoprotein secretion in a cellular model of human intestinal epithelium. Methods: CaCo‐2 cells were cultured to postconfluency in Transwell filters and stimulated with glucose (25 mM) in the presence or absence of insulin (100 nM) at their basolateral surface. SR‐BI mRNA and protein levels were quantified by quantitative reverse transcription‐PCR and immunoblot, respectively. Polarized localization of SR‐BI was determined by cell surface proteins biotinylation and streptavidin precipitation. Activities of PI3K, AKT, mTOR, and SR‐BI were pharmacologically antagonized. Cholesterol uptake was assessed by NBD‐cholesterol incorporation. Apolipoprotein (apo) B concentration was quantified by ELISA. Subcellular localization of neutral lipids (BODIPY) and SR‐BI (immunofluorescence) was determined by confocal microscopy. Results: In polarized CaCo‐2 cells, insulin increased SR‐BI at the mRNA and protein levels. SR‐BI was exclusively present at apical cell surface, as indicated by biotinylation and confocal microscopy analysis. Glucose did not modify SR‐BI abundance or subcellular localization. Effects of insulin on SR‐BI levels were abrogated by PI3K, AKT, or mTOR pharmacological antagonism. Cholesterol uptake, neutral lipid abundance, and apo B secretion were increased by insulin in CaCo‐2 cells, and these effects were prevented by SR‐BI pharmacological antagonism with block lipid transport‐1. Conclusions: insulin promotes cholesterol uptake, intracellular lipid store, and apo B–containing lipoproteins secretion by SR‐BI‐dependent mechanisms in a model of human intestinal epithelium.

show abstract

Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI

Cited by 6 publications

References 0 publications

Retracted: Advances in the physiological and pathological implications of cholesterol

Retracted: Advances in the physiological and pathological implications of cholesterol

The Alcohol–High-Density Lipoprotein Athero-Protective Axis

Insulin increases cholesterol uptake, lipid droplet content, and apolipoprotein B secretion in CaCo‐2 cells by upregulating SR‐BI via a PI3K, AKT, and mTOR‐dependent pathway

Contact Info

Product

Resources

About